REVERTANT DCIS IN HUMAN AXILLARY BREAST-CARCINOMA METASTASES

Recent experimental evidence obtained in Scid mice has suggested that the metastatic process is in large part epigenetically regulated and u ndergoes partial reversion once the metastatic process is completed: t he metastatic colonies become more engaged in the process of growing i a situ than actively metastasizing, Based on this experimental evidenc e, examples were sought of metastatic human cancers where similar reve rsion to an in situ growth state was occurring, Review of 200 cases of metastatic human breast cancer revealed a 21 per cent incidence of re version to a ductal carcinoma in situ (DCIS) growth pattern within axi llary nodal metastases. The revertant I)CIS areas were characterized b y an intact and circumferential basement membrane, as demonstrated by extracellular laminin and type IV collagen immunoreactivity. These rev ertant DCIS areas could be distinguished from primary DCIS, however, b y the absence of surrounding; myoepithelial cells in the former, ident ified in the latter by their positive maspin, S-100, and smooth muscle actin immunoreactivity. The pattern of revertant I)CIS, poorly differ entiated (comedo) (13 per cent), intermediate (non-comedo) (6 per cent ), or well-differentiated (non-comedo) (2%), exhibited complete 100 pe r cent concordance with the primary DCIS pattern, The concordance of h istological patterns held true for even the subtypes of DCIS determine d by architectural pattern, such as the micropapillary or cribriform s ubtypes, Nuclear size by digital image analysis and Her-2/neu, p53, an d Ki-67 status in the revertant DCIS also exhibited complete concordan ce nifh the primary DCIS counterparts, Cases exhibiting a revertant DC IS pattern tended to be ER-negative/EGFR-positive and exhibited signif icant nodal involvement (mean number, 9; mean area, 90 per cent) compa red with cases lacking a revertant pattern (mean number, 4; mean area, 15 per cent) (<0.01 ) These findings suggest that reversion of the me tastatic phenotype may also be occurring within autochthonous human me tastasis, (C) 1997 John Wiley & Sons, Ltd.